Imaging and pharmacokinetics of (64)Cu-DOTA-HB22.7 administered by intravenous, intraperitoneal, or subcutaneous injection to mice bearing non-Hodgkin's lymphoma xenografts.
OBJECTIVE
The aim of the study is to compare the tumor-specific targeting, pharmacokinetics, and biodistribution of (64)Cu-DOTA-HB22.7 when administered to xenograft-bearing mice intravenously (IV), intraperitoneally (IP), and subcutaneously (SQ).


METHODS
Mice bearing human non-Hodgkin's lymphoma (NHL) xenografts were injected IV, IP, or SQ with (64)Cu-DOTA-HB22.7. Xenograft targeting was evaluated by micro positron emission tomography (microPET) and confirmed by organ biodistribution studies. Blood measurements of (64)Cu were performed to determine the pharmacokinetics and clearance of (64)Cu-DOTA-HB22.7.


RESULTS
(64)Cu-DOTA-HB22.7 demonstrated equivalent tumor targeting within 24-48 h, regardless of the route of administration. Organ biodistribution confirmed tumor-specific targeting. Blood pharmacokinetics demonstrated that (64)Cu-DOTA-HB22.7 accessed the bloodstream after IP and SQ administration to a similar degree as IV administration, albeit at a slower rate.


CONCLUSIONS
These findings establish (64)Cu-DOTA-HB22.7 as a potential radioimmunotherapeutic and/or NHL-specific imaging agent. These findings provide evidence that IP and SQ administration can achieve results equivalent to IV administration and may lead to more efficient, reproducible treatment plans for antibody-based therapeutics.
Martin
Shiloh M
SM
Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis Cancer Center, Davis, CA, USA.
O'Donnell
Robert T
RT
Kukis
David L
DL
Abbey
Craig K
CK
McKnight
Hayes
H
Sutcliffe
Julie L
JL
Tuscano
Joseph M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005434:Flow Cytometry; D018796:Immunoconjugates / Q000008:administration & dosage / Q000493:pharmacokinetics; D007267:Injections; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013388:Succinimides / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; C502492:DOTA-NHS; D018796:Immunoconjugates; D019275:Radiopharmaceuticals; D013388:Succinimides